Cortexyme’s ongoing Phase 2/3 GAIN clinical trial, which is evaluating the investigational treatment COR388 (atuzaginstat) in people with mild to moderate Alzheimer’s disease, has been approved to continue as planned to its one-year endpoint, the company said.
Topline results from the study, testing whether COR388 can lessen dementia and neurodegeneration in Alzheimer’s, are expected on time in December 2021.
The trial recommendation was given by the independent Data Monitoring Committee (DMC) — a panel of independent scientists who monitor trial conduct and safety — after a pre-planned interim analysis of data that included about 300 patients who have received treatment for six months.
The DMC assessed criteria including safety, primary outcome efficacy, whether the number of participants is sufficient, and the overall likelihood the therapy will produce significant benefits (futility). The company remains blinded to the results.
“Given the tremendous unmet need in Alzheimer’s disease, it is imperative that we rapidly and efficiently study potential new treatments,” Marwan Sabbagh, MD, director of the Cleveland Clinic Center for Brain Health and GAIN’s principal investigator, said in a press release.
“We look forward to completing the study and sharing the results with the medical community and patients when the full trial results become available,” Sabbagh said.
Michael Detke, MD, PhD, Cortexyme’s chief medical officer, said the company was pleased with the DMC recommendation, “which we believe supports the study design and statistical powering of the GAIN Trial.”
GAIN (NCT03823404), which now has enrolled 643 participants ages 55 to 80, is a randomized, placebo-controlled study evaluating 40 and 80 mg of COR388, or a placebo, given twice daily to people with confirmed mild to moderate Alzheimer’s disease.
COR388 is designed to block enzymes secreted by the bacteria P. gingivalis, called gingipains, found in more than 90% of post-mortem brain samples from Alzheimer’s patients. These enzymes also have been shown to trigger Alzheimer’s pathology and neurodegeneration in animal models.
“The totality of evidence around P. gingivalis and gingipain inhibition shows that blocking this upstream target may impact multiple aspects of disease progression and neurodegeneration,” Detke said.
Following a six-week screening period, COR388 treatment continues for a total of 48 weeks (nearly one year). Patients then have a safety follow-up period of six weeks.
There are two primary endpoints in GAIN. One is a mean change in the Alzheimer’s Disease Assessment Scale-Cognitive Subscale 11 (ADAS-Cog 11), which measures cognitive and non-cognitive functions such as mood and behavior. The other goal is a change in the Clinical Dementia Rating-Sum of Boxes (CDR-SB), which measures dementia severity.
Secondary and exploratory endpoints include a change in the Activities of Daily Living (ADCS-ADL) assessment, Neuropsychiatric Inventory (behavioral disturbances), Mini-Mental State Examination (cognitive function), and a Winterlight speech assessment (a speech-based cognitive assessment).
In addition, along with undergoing magnetic resonance imaging (MRI) scans, patients will provide saliva and blood samples. Researchers also will test samples of the participants’ cerebrospinal fluid, which surrounds the brain and spinal cord. All samples will be tested for biomarkers, neuroinflammation, and P. gingivalis.
The trial also includes a sub-study to evaluate the clinical benefit of COR388 in the treatment of periodontitis, an infection of the gums that is caused by P. gingivalis and gingipains. Of the patients enrolled so far in this sub-study, more than 90% had moderate to severe periodontitis at the beginning of the trial.
After one year, eligible participants may enroll in a follow-up study, in which all patients will receive COR388.
“We are grateful to the DMC, the trial investigators, and the patients and caregivers for their participation in the trial as the study continues to its 1-year endpoint,” Detke added.
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